Thursday, June 21, 2007

Should synthetic biologists patent their components?[This, a piece for Nature’s online muse column, is the first fruit of the wonderful workshop I attended last week in Greenland on the convergence of synthetic biology and nanotechnology. That explains the apparent non-sequitur of a picture – taken at midnight in Ilulissat, way above the Arctic Circle. Much more on this to follow…(I may run out of pictures). Anyway, this piece surely won’t survive at this length on the Nature web pages, so here it is in full.]

“For the first time, God has competition”, claimed environmental pressure organization the ETC Group two weeks ago. With this catchy headline, they aimed to raise the alarm about a patent on “the world’s first-ever human-made species”, a bacterium allegedly created “with synthetic DNA” in the laboratories of the Venter Institute in Rockville, Maryland.

ETC had discovered a US patent application (20070122826) filed last October by the Venter Institute scientists. The institute was established by genomics pioneer Craig Venter, and one of its goals is to make a microorganism stripped of all non-essential genes (a ‘minimal cell’) as a platform for designing living cells from the bottom up.

ETC’s complaint was a little confused, because it could not figure out whether the synthetic bacterium, which the group dubbed ‘Synthia’, has actually been made. On close reading of the patent, however, it becomes pretty apparent that it has not.

Indeed, there was no indication that the state of the art had advanced this far. But it is a lot closer than you might imagine, as I discovered last week at a meeting in Greenland supported by the Kavli Foundation, entitled “The merging of bio and nano – towards cyborg cells.” Sadly, the details are currently under embargo – so watch this space.

However, the ETC Group was also exercised about the fact that Venter Institute scientists had applied for a patent on what it claimed were the set of essential genes needed to make a minimal organism – or as the application puts it, “for replication of a free-living organism in a rich bacterial culture medium.” These are a subset of the genes possessed by the microbe Mycoplasma genitalium, which has a total of just 485 genes that encode proteins.

If the patent were granted, anyone wanting to design an organism from the minimal subset of 381 genes identified by Venter’s team would need to apply for a license. “These monopoly claims signal the start of a high-stakes commercial race to synthesize and privatize synthetic life forms”, claimed ETC’s Jim Thomas. “Will Venter’s company become the ‘Microbesoft’ of synthetic biology?”

Now, that’s a better question (if rather hyperbolically posed). I’m told that this patent application has little chance of success, but it does raise an important issue. Patenting of genes has of course been a controversial matter for many years, but the advent of synthetic biology – of which a major strand involves redesigning living organisms by reconfiguring their genetic wiring – takes the debate to a new level.

“Synthetic biology presents a particularly revealing example of a difficulty that the law has frequently faced over the last 30 years – the assimilation of a new technology into the conceptual limits posed by existing intellectual property rights”, say Arti Rai and James Boyle, professors of law at Duke University in North Carolina in a recent article in the journal PLoS Biology [1]. “There is reason to fear that tendencies in the way that US law has handled software on the one hand and biotechnology on the other could come together in a ‘perfect storm’ that would impede the potential of the technology.”

What is new here is that genes are used in a genuine ‘invention’ mode, to make devices. Researchers have organized ‘cassettes’ of natural genes into modules that can be inserted into microbial genomes, giving the organisms new types of behaviour. One such module acted as an oscillator, prompting regular bursts of synthesis of a fluorescent protein. When added to the bacteria E. coli, it made the cells flash on and off with light [2].

It is arguably a distortion of the notion of ‘invention’ to patent a gene that exists in nature. But if you can start to make new ‘devices’ by arranging these genes in new ways, doesn’t that qualify? And if so, how small and rudimentary a ‘part’ becomes patentable?

At the Greenland conference, Drew Endy of the Massachusetts Institute of Technology admitted that the framework for ownership and sharing of developments in synthetic biology remains wholly unresolved. He and his MIT colleagues are creating a Registry of Standard Biological Parts to be used as the elements of genetic circuitry just like the transistors, capacitors and so forth.in electronics catalogues. This registry places the parts in the public domain, which can provide some protection against attempts to patent them.

Endy helps to organize an annual competition among university students for the design of engineered organisms with new functions. One of the recent entries, from students at the Universities of Texas at Austin and California at San Francisco, was a light-sensitive version of E. coli that could grow into a photographic film [3]. Endy says that these efforts would be impossibly expensive and slow if the intellectual property rights on all the components first had to be cleared.

He compares it to a situation where, in order to write a piece of computer code, you have to apply for licensing on each command, and perhaps on certain combinations of them too.

And in synthetic biology that sort of patenting seems disturbingly easy right now. “You can take any device from the Texas instruments TTL catalogue, put ‘genetically coded’ in front of it without reducing it to practice, and you have a good chance of getting a patent”, says Endy.

“Evidence from virtually every important industry of the twentieth century suggests that broad patents on foundational research can slow growth”, say Rai and Boyle. Bioengineer Jay Keasling of the University of California at Berkeley, who was also at the Greenland meeting, agrees that patenting has been a brake on the useful applications of biotechnology. He has been working for several years to engineer microbes to synthesize a compound called artemisinin, which is currently one of the best drugs available for fighting malaria4. Artemisinin is produced in tiny amounts by as Asian shrub. Extraction from this source is prohibitively expensive, making it impossible to use artemisinin to combat malaria in developing countries, where it kills 1-3 million people each year.

Keasling’s genetically engineered artemisinin could potentially be made at a fraction of the cost. But its synthesis involves orchestrating the activity of over 40 genetic components, which is a greater challenge than any faced previously in genetic engineering. He hopes that an industrial process might be up and running by 2009.

Scientists at the Venter Institute hope to make organisms that can provide cheap fuels from biomass sources, such as bacteria that digest plant matter and turn it into ethanol. When the ETC Group dismisses these efforts to use synthetic biology for addressing global problems as mere marketing strategies, they are grossly misjudging the researchers and their motives.

But might patenting pose more of a threat than twitchy pressure groups? “If you want to have a community sharing useful and good parts, 20 years of patent protection is obviously not helpful”, says Sven Panke of the ETH in Zürich, Switzerland, one of the organizers of the third Synthetic Biology conference being held there next week. “It would be very helpful if we could find a good way to reward but not impede.”

Endy points out that patenting is by no means the only way to protect intellectual property – although it is certainly one of the most costly, and so suits lawyers nicely. Copyright is another way to do it – although even that might now be too binding (thanks to the precedents set by Disney on Mickey Mouse), and it’s not obvious how it might work for synthetic biology anyway.

Tailormade contracts are another option, but Endy says they tend to be ‘leaky’. It may be that some form of novel, bespoke legal framework would work best, but that could be expensive too.

Intellectual property is prominently on the agenda at next week’s Zürich conference. But Panke says “we are going to take a look at the issue, but we will not solve it. In Europe we are just starting to appreciate the problem.”